Expression pattern of serine protease inhibitor kazal type 3 (Spink3) during mouse embryonic development

Abstract

Recent evidence shows that the serine protease inhibitor Kazal type 3 (Spink3) has more diverse functions than expected. To gain insight into its function, we analyzed the spatiotemporal expression profile of Spink3, using in situ hybridization (ISH) and a Spink3+/lacZ knock-in mouse, in which lacZ was inserted into the Spink3 locus. Spink3lacZ expression was first observed in the foregut, midgut, hindgut and the forebrain/midbrain junction region at 9.5 days post coitus (dpc). In the pancreas, Spink3 mRNA was detected at 11.5 dpc, before formation of the typical shape of the exocrine structure of the pancreas. Acinar cell expression was clearly identified by 13.5 dpc. After differentiation of the intestinal tract, Spink3lacZ expression was observed in the large intestine at 11.5 dpc, followed by expression in the small intestine at 13.5 dpc, before appearance of intestinal digestive enzymes. Spink3 mRNA and Spink3lacZ activity were also detected in other tissues, including the mesonephric tubules and the urogenital ridge at 11.5 dpc, the genital swelling at 13.5 dpc, the ductus epididymis at 17.5 dpc, and the seminal vesicle at 8 weeks. These data suggest that Spink3 may play important roles in proliferation and/or differentiation of various cell types during development.

SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer

“…However, when the gastrointestinal tract is inflamed, SPINK1 is involved in the regenerative process at the gastric ulcer edge and is strongly expressed within the ulcer-associated cell lineage in patients with IBD (11,12). In addition, we also observed Spink3 in the large intestine at 11.5 days postconception, an earlier stage of development, thus Spink3 influences the proliferation of colonic epithelial cells (8). Furthermore, Ogawa and colleagues (13,14) found elevated serum SPINK1 levels in patients with severe systemic inflammation.…”

“…In the gastrointestinal tract, Spink3 is most strongly expressed in the sigmoid colon and rectum at the embryonic stage (8). In addition, we previously revealed that the epithelial of the duodenum and small intestine in Spink3 À/À mice were degenerated (5).…”

“…We previously generated a Spink3 lacZ/þ knock-in mouse using a Cre recombination strategy (8). To determine Spink3 promoter activity, we detected the activity of b-galactosidase produced by the knock-in lacZ reporter gene in colon tissues.…”

“…To determine Spink3 promoter activity, we detected the activity of b-galactosidase produced by the knock-in lacZ reporter gene in colon tissues. The protocol of X-gal staining has been described previously (8). For each experiment, rigorous controls were carried out simultaneously in Spink3 wild-type mice to assay background endogenous b-galactosidase activity.…”

“…The role of SPINK1 is postulated to be the prevention of inadvertent proteolysis in the pancreas caused by intra-acinar premature activation of trypsinogen (4)(5)(6). However, it is known that SPINK1 is widely expressed in extrapancreatic tissues, especially in the gastrointestinal and urinary tracts (7,8), suggesting that SPINK1 has additional functions in many tissues other than the pancreas.…”